scholarly journals Regulatory function of simian virus 40 DNA replication for late viral gene expression.

1977 ◽  
Vol 74 (11) ◽  
pp. 4831-4834 ◽  
Author(s):  
A. Graessmann ◽  
M. Graessmann ◽  
C. Mueller
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Viral Gene Expression ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Regulatory Function ◽  
Viral Gene

scholarly journals Contribution of DNA Replication to the FAM111A-Mediated Simian Virus 40 Host Range Phenotype

2018 ◽  
Vol 93 (1) ◽  
Author(s):  
Roxana M. Tarnita ◽  
Adrian R. Wilkie ◽  
James A. DeCaprio
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Viral Replication ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Host Protein ◽  
Viral Gene ◽  
Viral Dna ◽  
Viral Dna Replication

ABSTRACTHost range (HR) mutants of simian virus 40 (SV40) containing mutations in the C terminus of large T antigen fail to replicate efficiently or form plaques in restrictive cell types. HR mutant viruses exhibit impairments at several stages of the viral life cycle, including early and late gene and protein expression, DNA replication, and virion assembly, although the underlying mechanism for these defects is unknown. Host protein FAM111A, whose depletion rescues early and late gene expression and plaque formation for SV40 HR viruses, has been shown to play a role in cellular DNA replication. SV40 viral DNA replication occurs in the nucleus of infected cells in viral replication centers where viral proteins and cellular replication factors localize. Here, we examined the role of viral replication center formation and DNA replication in the FAM111A-mediated HR phenotype. We found that SV40 HR virus rarely formed viral replication centers in restrictive cells, a phenotype that could be rescued by FAM111A depletion. Furthermore, while FAM111A localized to nucleoli in uninfected cells in a cell cycle-dependent manner, FAM111A relocalized to viral replication centers after infection with SV40 wild-type or HR viruses. We also found that inhibition of viral DNA replication through aphidicolin treatment or through the use of replication-defective SV40 mutants diminished the effects of FAM111A depletion on viral gene expression. These results indicate that FAM111A restricts SV40 HR viral replication center formation and that viral DNA replication contributes to the FAM111A-mediated effect on early gene expression.IMPORTANCESV40 has served as a powerful tool for understanding fundamental viral and cellular processes; however, despite extensive study, the SV40 HR mutant phenotype remains poorly understood. Mutations in the C terminus of large T antigen that disrupt binding to the host protein FAM111A render SV40 HR viruses unable to replicate in restrictive cell types. Our work reveals a defect of HR mutant viruses in the formation of viral replication centers that can be rescued by depletion of FAM111A. Furthermore, inhibition of viral DNA replication reduces the effects of FAM111A restriction on viral gene expression. Additionally, FAM111A is a poorly characterized cellular protein whose mutation leads to two severe human syndromes, Kenny-Caffey syndrome and osteocraniostenosis. Our findings regarding the role of FAM111A in restricting viral replication and its localization to nucleoli and viral replication centers provide further insight into FAM111A function that could help reveal the underlying disease-associated mechanisms.

scholarly journals Elements in the immunoglobulin heavy-chain enhancer directly regulate simian virus 40 ori-dependent DNA replication.

1993 ◽  
Vol 13 (9) ◽  
pp. 5629-5636 ◽  
Author(s):  
K Ariizumi ◽  
M R Ghosh ◽  
P W Tucker
Keyword(s):  
Dna Replication ◽  
Heavy Chain ◽  
Direct Interaction ◽  
Simian Virus 40 ◽  
Immunoglobulin Heavy Chain ◽  
Simian Virus ◽  
Regulatory Function ◽  
Chromosomal Dna ◽  
Chromosomal Replication ◽  
Sv40 Dna

In a previous study, we showed that the immunoglobulin heavy-chain (IgH) enhancer (IgHe) is near or in an initiation zone of chromosomal DNA replication, which is preferentially active in B cells (K. Ariizumi, Z. Wang, and P. W. Tucker, Proc. Natl. Acad. Sci. USA 90:3695-3699, 1993). This suggests the existence of a functional relationship between IgHe-mediated transcription and DNA replication. To test this theory, we utilized simian virus 40 (SV40) DNA replication as a model of chromosomal replication. IgHe or its operationally divisible domains (5'-En, core, and 3'-En) were introduced into SV40 minichromosomes (IgHe-SV40). Results of replication assays with IgHe-SV40 replicons indicated that the 5'-En and 3'-En activated or suppressed SV40 DNA replication regardless of the presence of SV40 enhancers or promoters in these replicons. The activity did not reside in IgHe core sequences. The results suggested that the 5'- and 3'-En regulated SV40 replication through direct interaction with the origin, not through suppression at the SV40 enhancer and/or promoter. In an effort to identify elements within the 5'-En motif that contributed to this effect, we found that the E site, but not microE5 and microE2 boxes, upregulated DNA replication. Our results provide another possible regulatory function for the 5'-En and 3'-En domains besides transcriptional suppression of IgHe.

T4 DNA replication and viral gene expression

1971 ◽  
Vol 61 (2) ◽  
pp. 357-367 ◽  
Author(s):  
A. Cascino ◽  
E.P. Geiduschek ◽  
R.L. Cafferata ◽  
R. Haselkorn
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Viral Gene Expression ◽  
Viral Gene

scholarly journals Independent Contributions of Polyomavirus Middle T and Small T to the Regulation of Early and Late Gene Expression and DNA Replication

2006 ◽  
Vol 80 (15) ◽  
pp. 7295-7307 ◽  
Author(s):  
Li Chen ◽  
Xiaoyu Wang ◽  
Michele M. Fluck
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Signaling Pathways ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Phosphatidylinositol 3 Kinase ◽  
Late Gene Expression ◽  
Respective Contribution ◽  
Mouse Cells ◽  
The Individual

ABSTRACT We previously showed that murine polyomavirus mutants that lack both middle T (MT) and small T (ST) functions have a severe pleiotropic defect in early and late viral gene expression as well as genome amplification. The respective contribution of MT and ST to this phenotype was unclear. This work separates the roles of MT and ST in both permissive mouse cells and nonpermissive rat cells. It demonstrates for the first time a role for both proteins. To gain insight into the signaling pathways that might be required, we focused on MT and its mutants. The results show that each of the major MT signaling connections, Shc, phosphatidylinositol 3′-kinase, and phospholipase C γ1, could contribute in an additive way. Unexpectedly, a mutant lacking all these connections because the three major tyrosines had been converted to phenylalanine retained some activity. A mutant in which all six MT C-terminal tyrosines had been mutated was inactive. This suggests a novel signaling pathway for MT that uses the minor tyrosines. What is common to ST and the individual MT signaling pathways is the ability to signal to the polyomavirus enhancer, in particular to the crucial AP-1 and PEA3/ets binding sites. This connection explains the pleiotropy of MT and ST effects on transcription and DNA replication.

scholarly journals Naturally arising recombinants that are missing portions of the simian virus 40 regulatory region.

1983 ◽  
Vol 3 (11) ◽  
pp. 1930-1936 ◽  
Author(s):  
M Woodworth-Gutai ◽  
A Celeste ◽  
L Sheflin ◽  
M Sclair
Keyword(s):  
Nucleotide Sequence ◽  
Replication Origin ◽  
Regulatory Region ◽  
Viral Gene Expression ◽  
Simian Virus 40 ◽  
Serial Passage ◽  
Simian Virus ◽  
Viral Gene ◽  
Nucleotide Sequence Level ◽  
Sequence Elements

When simian virus 40 (SV40) is serially passaged at high multiplicity, a heterogeneous collection of naturally arising variants is generated. Those which are the most abundant presumably have a selective replicative advantage over other defective and wild-type helper SV40s. Two such naturally arising host-substituted variants of SV40 have been characterized in terms of complete nucleotide sequence determination. Evolutionary variant ev-1101 (previously isolated by Lee et al., Virology 66:53-69, 1975) is from undiluted serial passage 13, whereas ev-2101 is newly isolated from undiluted serial passage 6 of an independently-derived evolutionary series. Both variants contain a five-times tandemly repeated segment of DNA consisting of viral Hin C and Hin A sequences that have recombined with a segment of host DNA that is not highly reiterated in the monkey genome. The monkey segment differs in the two variants as does the size of the viral segment retained. In two additional host-substituted variants, ev-1102 (previously isolated from serial passage 20 by Brockman et al., Virology 54:384-397, 1973) and ev-1108 (newly isolated from serial passage 40), the SV40 sequences derived from the replication origin are present as inverted repetitions. The inverted repeat regions of these two variants have been analyzed at the nucleotide sequence level and are compared with SV40 variant ev-1104 from passage 45 (previously characterized by Gutai and Nathans, J. Mol. Biol. 126:259-274, 1978). The viral segment containing the regulatory signals for replication and viral gene expression is considerably shortened in later serial passages as demonstrated by these five variants. It is of interest that the variants presumably arose due to their enhanced replication efficiency, yet are missing some of the sequence elements implicated in the regulation of replication. Furthermore, a comparison of the structure of the replication origin regions indicates that additional changes occur in the SV40 regulatory region with continued undiluted serial passage.

scholarly journals Kaposi's Sarcoma-Associated Herpesvirus K-bZIP Protein Is Necessary for Lytic Viral Gene Expression, DNA Replication, and Virion Production in Primary Effusion Lymphoma Cell Lines

2009 ◽  
Vol 83 (11) ◽  
pp. 5869-5880 ◽  
Author(s):  
Sylvain Lefort ◽  
Louis Flamand
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Kaposi's Sarcoma ◽  
Viral Gene Expression ◽  
Kaposi’S Sarcoma ◽  
Viral Gene ◽  
Viral Dna ◽  
Viral Dna Replication ◽  
Virion Production ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of three human proliferative disorders, namely, Kaposi's sarcoma, primary effusion lymphomas (PEL), and multicentric Castleman's disease. Lytic DNA replication of KSHV, which is essential for viral propagation, requires the binding of at least two KSHV proteins, replication and transactivation activator (RTA) and K-bZIP, on the lytic origin of replication. Moreover, K-bZIP physically interacts with RTA and represses its transactivation activity on several viral promoters in transient transfection assays. To evaluate the physiological roles of K-bZIP in the context of PEL, we generated BCBL-1 cells with a tetracycline (Tet)-inducible small hairpin RNA (shRNA) directed against the K8 mRNA to knock down K-bZIP expression at different points during KSHV's life cycle. Using this model, we demonstrate that in the absence of K-bZIP expression, dramatic decreases in orf50, orf57, and orf26 transcript expression are observed. Similar effects were seen at the protein level for RTA (immediate-early protein) and K8.1 (late protein) expression. Interestingly, a direct correlation between K-bZIP levels and viral lytic mRNAs was noticed. As a consequence of K-bZIP knockdown, viral DNA replication and virion production were severely impaired. The same effects were observed following knockdown of K-bZIP in another PEL cell line, BC3. Finally, using shRNA-K8-inducible 293 cells, we report that de novo synthesis of K-bZIP is not necessary for initiation of infection and latency establishment. These data support the concept that K-bZIP is essential for lytic viral gene expression, viral DNA replication, and virus propagation in PEL cells.

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